The overall aim of this proposal is to develop a freely available, extensible finite element modeling framework for solid mechanics, fluid mechanics, solute transport, and electrokinetics in biological cells, tissues and organs. To date, no such tools are available for general use in the public domain. All development will be designed specifically to meet the needs of research in the field of computational biomechanics. All development will based around our nonlinear implicit finite element software FEBio and the associated pre- and postprocessors, PreView and PostView. In Aim 1, we will extend the FEBio finite element framework to the representation of mixtures consisting of solid matrix, solvent, and any number of solutes. Aim 2 will focus on development and implementation of algorithms to represent contact between solids and mixtures having a solid matrix, properly accounting for conservation of mass and momentum between contacting mixtures. To accommodate automatic tetrahedral mesh generation, Aim 3 will implement a robust, enhanced-strain tetrahedral element in FEBio that can accommodate the physics of both solids and mixtures. In Aim 4, we will expand our existing pre- and postprocessing software packages to support tetrahedral mesh generation, specification of boundary conditions on mixtures, anisotropic solid matrix and transport properties, and variable mixture constituents. Finally, Aim 5 will provide mechanisms for user and developer support, software distribution, verification and dissemination of FEBio. Accurate, quantitative simulations of the biomechanics and biophysics of living systems and their surrounding environment have the potential to facilitate advancements in nearly every aspect of medicine and biology. The results of this project will yield a powerful and essential modeling framework for research in biomechanics and biophysics, with the ability to address applications that span the missions of the NIH Institutes. PUBLIC HEALTH RELEVANCE: The overall aim of this application is to develop a freely available, extensible finite element modeling framework for solid mechanics, fluid mechanics, solute transport, and electrokinetics in biological cells, tissues and organs, based around the FEBio framework. The results of this research will provide a powerful and essential modeling software tool for biomechanics and provide a common platform for all bioengineers, with applications that span the missions of the NIH Institutes. [unreadable] [unreadable] [unreadable]